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Background: Sickle cell disease (SCD) is a group of genetic blood disorders characterized by a single point mutation in the sixth codon of the β-globin gene. Under low oxygen tension, the resultant abnormal hemoglobin S polymerizes and causes rigid and sickle-shaped red blood cells.Objectives: This study aimed to assess the effect of omega-3 supplementation in patients with sickle cell anemia.Subjects and methods: Seventy-eight SCD patients, who were undergoing regular follow-up at the outpatients SCD clinic in Ibn-Aoaf Pediatrics and Khartoum hospitals, were the main study group and 35 individuals were selected as control group. Patients recruited randomly were assigned to receive omega-3 fatty acid supplementation for at least two years. 5 ml of venous blood was collected from every individual into EDTA test tubes and used to determine complete blood count (CBC), electrophoresis and reticulocyte count.Results: A significant difference in the Hb (g/dl) mean between the omega-3 group and the group free of omega-3 (P. value < 0.0001) was recorded. Also in total red blood cells count X 103C/M l, hematocrit and mean cell hemoglobin pg (P.value < 0.05) .No difference in levels between the study groups at mean cell volume / f l and mean cell hemoglobin concentration % (P. value < 0.05). Retics count and reticulocyte production index significant decrease in omega-3 group compared to control group (P.value < 0.0001).Conclusions: These findings suggest that omega-3 fatty acids can be an effective, safe, and affordable therapy for sickle cell anemia.